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红霉素对大鼠永久性局灶性脑缺血后缺血性损伤的神经保护作用。

Neuroprotective effects of erythromycin on ischemic injury following permanent focal cerebral ischemia in rats.

作者信息

Katayama Yasuo, Inaba Toshiki, Nito Chikako, Ueda Masayuki

机构信息

a Department of Neurology and Stroke Center , Tokyo General Hospital , Tokyo , Japan.

b Graduate School of Medicine , Nippon Medical School , Tokyo , Japan.

出版信息

Neurol Res. 2016 Mar;38(3):275-84. doi: 10.1080/01616412.2016.1138662. Epub 2016 Mar 16.

Abstract

OBJECTIVE

This study aims to determine if erythromycin provides neuroprotective effects against ischemic injury following permanent focal cerebral ischemia.

METHODS

Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Each animal received a single subcutaneous injection of erythromycin lactobionate (EM, 50 mg/kg) or vehicle immediately after ischemia. The infarct volume, edema index and neurological performance were evaluated at 24 and 72 h after MCAO. The cerebral blood flow (CBF) was measured with an MRI system at 30 min after MCAO. TUNEL staining and immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) in the cortex were conducted at 24 and 72 h after MCAO.

RESULTS

The CBF did not differ between the EM-treated and vehicle-treated groups. The EM treatment significantly reduced the infarct volume (p < 0.01) at 24 and 72 h after MCAO and significantly reduced the edema index (p < 0.01) at 24 h. The EM treatment significantly improved the neurological deficit scores (p < 0.05) at 24 and 72 h. EM also significantly suppressed the accumulation of 4-HNE (p < 0.01) and 8-OHdG (p < 0.01) and markedly reduced Iba-1 (p < 0.01) and TNF-α expression (p < 0.05) at both time points. The EM treatment significantly reduced TUNEL-positive cells (p < 0.01) at both time points.

CONCLUSION

These findings suggest that EM can protect against the neuronal damage caused by cerebral ischemia by alleviating inflammation and reducing oxidant stress.

摘要

目的

本研究旨在确定红霉素是否对永久性局灶性脑缺血后的缺血性损伤具有神经保护作用。

方法

将Sprague-Dawley大鼠进行大脑中动脉闭塞(MCAO)。每只动物在缺血后立即皮下注射一次乳糖酸红霉素(EM,50mg/kg)或赋形剂。在MCAO后24小时和72小时评估梗死体积、水肿指数和神经功能。在MCAO后30分钟用MRI系统测量脑血流量(CBF)。在MCAO后24小时和72小时对皮质进行TUNEL染色以及氧化应激(4-HNE、8-OHdG)和炎症(Iba-1、TNF-α)的免疫组织化学分析。

结果

EM治疗组和赋形剂治疗组之间的CBF没有差异。EM治疗在MCAO后24小时和72小时显著减小了梗死体积(p<0.01),并在24小时显著降低了水肿指数(p<0.01)。EM治疗在24小时和72小时显著改善了神经功能缺损评分(p<0.05)。在两个时间点,EM还显著抑制了4-HNE(p<0.01)和8-OHdG(p<0.01)的积累,并显著降低了Iba-1(p<0.01)和TNF-α表达(p<0.05)。EM治疗在两个时间点均显著减少了TUNEL阳性细胞(p<0.01)。

结论

这些发现表明,EM可通过减轻炎症和降低氧化应激来保护免受脑缺血引起的神经元损伤。

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